122 results about "Caspase inhibitors" patented technology

This invention provides caspase inhibitors having the formula:wherein Ring A is an optionally substituted piperidine, tetrahydroquinoline or tetrahydroisoquinoline ring; R1 is hydrogen, CHN2, R, or —CH2Y; R is an optionally substituted group selected from an aliphatic group, an aryl group, an aralkyl group, a heterocyclic group, or an heterocyclylalkyl group; Y is an electronegative leaving group; R2 is CO2H, CH2CO2H, or esters, amides or isosteres thereof; Ar is an optionally substituted aryl group; and R3 is hydrogen, an optionally substituted C1-6 alkyl, F2, CN, aryl or R3 is attached to Ar to form an unsaturated or partially saturated five or six membered fused ring having 0–2 heteroatoms. The compounds are useful for treating caspase-mediated diseases in mammals.

The present invention provides methods, compositions and devices for stabilizing the extracellular nucleic acid population in a cell-containing biological sample using an apoptosis inhibitor, preferably a caspase inhibitor, a hypertonic agent and / or a compound according to formula (1) as defined in the claims.

The invention relates to processes and compounds useful for producing modified aspartic acid derivatives, such as aspartic acid aldehyde moieties. Aspartic acid derivatives are useful for preparing caspase inhibitors and / or prodrugs thereof.

Disclosed herein is a method for making compounds that are useful as caspase inhibitor prodrugs of formula I: wherein R1 is an optionally substituted group selected from an aliphatic group, aralkyl group, heterocyclylalkyl group or aryl group, and R2 is preferably a P2—P4 moiety of a caspase inhibitor. Key intermediates include the azidolactones III and VIII:

The present invention provides a compound of formula I: wherein R1, R2, R3, R4, and R5 are as defined herein. The present invention also provides pharmaceutical compositions and methods using such compositions for treating a caspase-mediated diseases and processes for preparting the compounds of the invention.

The present invention relates to a pharmaceutical composition comprising a caspase inhibitor and / or a compound of the general formula R-Lys-X, methods for coating medical products using said caspase inhibitors and / or said compounds of general formula R-Lys-X and medical products coated with said caspase inhibitors and / or said compounds of general formula R-Lys-X.

This invention provides compounds of formula I:wherein Z is oxygen or sulfur; R1 is hydrogen, —CHN2, R, CH2OR, CH2SR, or —CH2Y; next to R3 represents a single or double bond; Y is an electronegative leaving group; R2 is CO2H, CH2CO2H, or esters, amides or isosteres thereof; R3 is a group capable of fitting into the S2 subsite of a caspase enzyme; R4 is a hydrogen or C1-6 alkyl or R3 and R4 taken together form a ring; Ring A and Ring B are each heterocyclic rings, and R and R5 are as described in the specification. The compounds are effective inhibitors of apoptosis and IL-1β secretion.

The present invention provides a compound of formula I:wherein the variables are as defined herein. The present invention also provides processes for preparing the compounds of formula I, and intermediates thereof, pharmaceutical compositions comprising those compounds, and methods of using the compounds and compositions.

The present invention provides a compound of formula I:wherein:X is —OR1 or —N(R5)2,Y is halo, trifluorophenoxy, or tetrafluorophenoxy;R1 is:C1-6 straight chained or branched alkyl, alkenyl, or alkynyl, wherein the alkyl, alkenyl, or alkynyl is optionally substituted with optionally substituted aryl, CF3, Cl, F, OMe, OEt, OCF3, CN, or NMe2;C1-6 cycloalkyl, wherein 1-2 carbon atoms in the cycloalkyl is optionally replaced with —O— or —NR5—;R2 is C1-6 straight chained or branched alkyl;R3 is hydrogen, halo, OCF3, CN, or CF3;R4 is hydrogen, halo, OCF3, CN, or CF3; andeach R5 is independently H, C1-6 straight chained or branched alkyl, aryl, —O—C1-6 straight chained or branched alkyl, or —O-aryl.The present invention also provides pharmaceutical compositions and methods using such compositions for treating a caspase-mediated disease, particularly in the central nervous system.

Provided are to a freezing medium composition for cryopreserving amniotic fluid-derived stem cells, which has A lower concentration of Me2SO and eliminates fetal bovine serum and at the same time does not induce cryoinjury to fluid-derived stem cells and makes it possible to cryopreserve fluid-derived stem cells for a prolonged time using trehalose, sucrose and catalase, and a method for cryopreserving the same. According to the present invention, AFSCs can be cryopreserved with 1 / 4 the standard Me2SO concentration with the addition of disaccharides, antioxidants and caspase inhibitors. As a result, the use of Me2SO at low concentrations in cell freezing solutions may support the development of clinical trials of AFSCs.

The present invention provides a compound of formula wherein the variables are as defined herein. The present invention also provides processes for preparing the compounds of formula I, and intermediates thereof, pharmaceutical compositions comprising those compounds, and methods of using the compounds and compositions.

The invention relates to novel diazoketone derivatives. The invention also relates to processes for homologation of these diazoketone derivatives. The processes are useful for preparing compounds that are caspase inhibitors.

The present invention relates to novel classes of compounds of formula I which are caspase and TNF-alpha inhibitors. This invention also relates to pharmaceutical compositions comprising these compounds. The compounds and pharmaceutical compositions of this invention are particularly well suited for inhibiting caspase and TNF-alpha activity and consequently, can be advantageously used as agents against caspase-, interleukin-1-(“IL-1”), apoptosis-, interferon-γ inducing factor-(IGIF), interferon-γ-(“IFN-γ”), or TNF-alpha mediated diseases, including inflammatory diseases, autoimmune diseases, destructive bone disorders, proliferative disorders, infectious diseases, and degenerative diseases. This invention also relates to processes for preparing the compounds of this invention. This invention also relates to methods for inhibiting caspase and TNF-alpha activity and decreasing IGIF production and IFN-γ production and methods for treating caspase-, interleukin-1, apoptosis-, and interferon-γ-, and TNF-alpha mediated diseases using the compounds and compositions of this invention.

The present invention provides a compound of formula I:wherein R1, R2, R3, R4, and R5 are as defined herein. The present invention also provides pharmaceutical compositions and methods using such compositions for treating a caspase-mediated diseases and processes for preparing the compounds of the invention.

The present invention relates to trans-capsularly administering into a diseased joint a high specificity antagonist selected from the group consisting of:i) an inhibitor of a pro-inflammatory interleukin;ii) an inhibitor of TNF-α synthesis;iii) an inhibitor of membrane-bound TNF-α;iv) an inhibitor of a natural receptor of TNF-α;v) an inhibitor of NO synthase,vi) an inhibitor of PLA2 enzyme;vii) an anti-proliferative agent;viii) an anti-oxidant;ix) an apoptosis inhibitor selected from the group consisting of EPO mimetic peptides, EPO mimetibodies, IGF-I, IGF-II, and caspase inhibitors, andx) an inhibitor of MMPs; andxi) an inhibitor of p38 kinase.